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http://dx.doi.org/10.5762/KAIS.2016.17.3.127

Cell proliferation inhibition effects of epigallocatechin-3-gallate in TREK2-channel overexpressing cell line  

Kim, Yangmi (Dept. of Physiology, College of Medicine, Chungbuk National University)
Kim, Kyung-Ah (Dept. of Biomedical Engineering, College of Medicine, Chungbuk National University)
Publication Information
Journal of the Korea Academia-Industrial cooperation Society / v.17, no.3, 2016 , pp. 127-135 More about this Journal
Abstract
Two-pore domain potassium (K2P) channels are the targets of physiological stimuli, such as intracellular pH, bioactive lipids, and neurotransmitters, and they set the resting membrane potential. Some types of K2P channels play a critical role in both apoptosis and tumoriogenesis. Among the K2P channels, no antagonists of the TREK2 channel have been reported. The aim of the present study was to determine if the TREK2 channel is blocked and whether cell proliferation is influenced by flavonoids in the TREK2 overexpressing HEK293 cells (HEKT2). The electrophysiological current was recorded using single channel patch clamp techniques and cell proliferation was measured using a XTT assay. The electrophysiological results showed that the TREK2 channel activity was reduced to $91.5{\pm}13.1%$ (n=5) and $82.2{\pm}13.7%$ (n=5) by flavonoids, such as epigallocatechin-3-gallate (EGCG) and quercetin in HEKT2 cells, respectively. In contrast, the EGCG analogue, epicatechin (EC), had no significant inhibitory effects on the TREK2 single channel activity. In addition, cell proliferation was reduced to $69.4{\pm}14.0%$ (n=4) by ECGG in the HEKT2 cells. From these results, EGCG and quercetin represent the first known TREK2 channel inhibitors and only EGCG reduced HEKT2 cell proliferation. This suggests that the flavonoids may work primarily by inhibiting the TREK2 channel, leading to a change in the resting membrane potential, and triggering the initiation of a change in intracellular signaling for cell proliferation. TREK2 channel may, at least in part, contribute to cell proliferation.
Keywords
Epigallocatechin-3-gallate(EGCG); Flavonoid; Quercetin; TREK2; Two-pore domain potassium(K2P) channels;
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